posted on 2020-03-04, 20:34authored byDnyaneshwar Kand, Pei Liu, Marisol X. Navarro, Logan J. Fischer, Liat Rousso-Noori, Dinorah Friedmann-Morvinski, Arthur H. Winter, Evan W. Miller, Roy Weinstain
Photoactivation of
bioactive molecules allows manipulation of cellular
processes with high spatiotemporal precision. The recent emergence
of visible-light excitable photoprotecting groups has the potential
to further expand the established utility of the photoactivation strategy
in biological applications by offering higher tissue penetration,
diminished phototoxicity, and compatibility with other light-dependent
techniques. Nevertheless, a critical barrier to such applications
remains the significant hydrophobicity of most visible-light excitable
photocaging groups. Here, we find that applying the conventional 2,6-sulfonation
to meso-methyl BODIPY photocages is incompatible
with their photoreaction due to an increase in the excited state barrier
for photorelease. We present a simple, remote sulfonation solution
to BODIPY photocages that imparts water solubility and provides control
over cellular permeability while retaining their favorable spectroscopic
and photoreaction properties. Peripherally disulfonated BODIPY photocages
are cell impermeable, making them useful for modulation of cell-surface
receptors, while monosulfonated BODIPY retains the ability to cross
the cellular membrane and can modulate intracellular targets. This
new approach is generalizable for controlling BODIPY localization
and was validated by sensitization of mammalian cells and neurons
by visible-light photoactivation of signaling molecules.